All India Institute of Medical Sciences, Rishikesh
Submittted/Under Review
Amala Institute of Medical Sciences
Approved
Institute of Medical Sciences & SUM Hospital
Submittted/Under Review
Malabar Cancer Centre
Submittted/Under Review
Meenakshi Mission Hospital & Research Centre
Submittted/Under Review
Mohandai Oswal Cancer Hospital
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Not Applicable
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C20||Malignant neoplasm of rectum,
Intervention / Comparator Agent
Type
Name
Details
Intervention
NIL
NIL
Comparator Agent
NIL
NIL
Inclusion Criteria
Age From
18.00 Year(s)
Age To
70.00 Year(s)
Gender
Both
Details
those with
ECOG Performance Status 0 to 2,
histologically confirmed rectal adenocarcinoma below the peritoneal reflection as per MRI,
cT4 or cN2, or MRF involvement, or EMVI.
ExclusionCriteria
Details
those with,
metastatic disease (M1),
prior malignancies within the last 5 years (excluding non-melanoma skin cancer),
contraindications to chemotherapy or radiotherapy,
bowel obstruction for whom emergency diversion is required,
uncontrolled systemic illness or cardiac dysfunction,
deemed unfit for TNT by the treating team.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Pathological Complete Response (pCR): Defined as no residual tumor in the surgical
specimen (ypT0N0) based on tumor regression score.
at 3, 6, 9, 12, 15, 18, 21, 24 months.
Secondary Outcome
Outcome
TimePoints
Acute Toxicity: Measured using CTCAE v5.0 for grade 3-4 toxicities during and after
treatment.
at 3, 6, 9, 12, 15, 18, 21, 24 months.
Disease-Free Survival (DFS): Time from diagnosis to locoregional or distant relapse, or
death from rectal carcinoma.
Total Sample Size="78" Sample Size from India="78" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
03/02/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="5" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
What data in particular will be shared? Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
What additional supporting information will be shared? Response - Study Protocol Response - Statistical Analysis Plan Response - Informed Consent Form Response - Clinical Study Report Response - Analytic Code
Who will be able to view these files? Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
For what types of analyses will this data be available? Response - For individual participant data meta-analysis.
By what mechanism will data be made available? Response - Proposals should be directed to [febinanthony@gmail.com].
For how long will this data be available start date provided 01-01-2030 and end date provided 01-01-2035? Response - Beginning 3 months and ending 5 years following article publication.
Any URL or additional information regarding plan/policy for sharing IPD? Additional Information - nil
Brief Summary
Locally advanced rectal cancer (LARC) with high-risk features, such as cT4 tumors, N2 lymph node involvement, mesorectal fascia involvement (MRF), and extramural vascular invasion (EMVI), presents significant treatment challenges. Preoperative long course chemo-radiation therapy (LCCRT) or short-course radiation therapy (SCCRT), which had been established as the standard of care, resulted in better local control. However, risk of loco regional failure (LRF) and distant metastases remained a concern. Consequently, postoperative chemotherapy was included in the treatment sequence, but patient adherence to this approach was poor, and it did not lead to an improvement in over all survival (OS).
Recently, total neoadjuvant therapy(TNT),combining neoadjuvant chemotherapy(NACT) with either SCCRT or LCCRT, has been suggested as a strategy to enhance adherence, reduce distant metastases, and potentially improve OS.
RAPIDO trial, first among the TNT trials, compared SCRT followed by two-drug NACT followed by total mesorectal excision to preoperative LCCRT and showed an improvement in disease-related treatment failure at 3 years 4. PRODIGE-23 trial used a three-drug intensive NACT followed by chemo radiation and total mesorectal excision followed by adjuvant chemotherapy and demonstrated improvement in disease free survival (DFS) at 3years. OPRA trial compared two-drug induction chemotherapy followed by LCCRT to LCCRT followed by two-drug consolidation chemotherapy, with patients either undergoing selective watchful waiting or TME as the next step and established a similar DFS in both the groups.
While critically analysing the above TNT trials, RAPIDO which used a short course RT had shown to have a numerically more LRF, PRODIGE which used a three-drug intensive NACT resulted in a slightly higher serious adverse event. And OPRA trial proved that a two- drug regimen as induction or consolidation in TNT can bring similar DFS. This highlights the need for a TNT protocol tailored to the Indian population, one that is well-tolerated and can be implemented in clinics without concerns and integrates the best aspects of existing TNT protocols. Interestingly most of the studies have left the option of adjuvant chemotherapy, it needs to be seen if patients can tolerate all the chemotherapy and concurrent chemo- radiation upfront and whether that would lead to improved outcomes with manageable toxicity profiles. This study aims to evaluate the efficacy and tolerability of a CTNT protocol, involving eight cycles of two-drug induction chemotherapy followed by LCCRT and surgery, with regard to pathological complete response (pCR) rates, grade 3-4 toxicities, LRF, DFS , and OS particularly for Indian population.